Objective Non-alcoholic steatohepatitis (NASH) is a major driver of malignant progression to hepatocellular carcinoma (HCC) and constitutes an independent risk factor for chronic kidney disease (CKD). The synergistic effects of NASH–HCC progression may exacerbate renal injury; moreover, the severity of NASH-associated nephropathy is positively correlated with the extent of hepatic fibrosis/cirrhosis. Nonetheless, the relationship between NASH–HCC and renal injury, together with its underlying pathogenic mechanisms, remains incompletely elucidated. Objective Using a novel murine NASH–HCC model (HRAS-HCC), this study aimed to characterize the renal injury, functional impairment, histopathological alterations, and molecular signatures accompanying hepatocarcinogenesis driven by NASH, thereby delineating potential mechanistic links between NASH–HCC and renal damage. Methods HRAS-HCC transgenic mice generated in-house were employed; littermate negative controls and wild-type C57BL/6 mice served as comparators. At 5 weeks of age, tamoxifen administration induced hepatocyte-specific HRAS expression, thereby initiating and propagating NASH–HCC. During disease progression (weeks 1–4), body weight, general condition, and behavioural parameters were monitored serially. Blood was collected at predetermined time points for biochemical analyses. Renal tissue was subjected to haematoxylin–eosin (H E) and Masson’s trichrome staining to evaluate structural and fibrotic changes. Results Within four weeks, HRAS-HCC mice transitioned from NASH through hepatic fibrosis to established HCC, manifesting jaundice, tachypnoea, kyphosis, haematochezia, hepatosplenomegaly, and other clinical signs. At week 4, serum alkaline phosphatase (ALP) was significantly decreased (P < 0.05), whereas blood urea nitrogen (BUN), uric acid (UA), and creatinine (CREA) were markedly elevated (P < 0.05). Histopathology revealed temporally heterogeneous renal lesions, including tubular basophilia, hyaline glomerulopathy, and tubular epithelial cytoplasmic hyaline droplet formation. Masson’s staining demonstrated renal fibrosis whose onset (weeks 2–3) and severity paralleled those of hepatic fibrosis/cirrhosis. Quantitative RT-PCR at week 3 showed up-regulation of keratin-18 (Krt18), Smad3, fibronectin (Fn), and transforming growth factor-β (Tgf-β) mRNA (P < 0.05). Protein–protein interaction (PPI) analyses further indicated direct interactions among human HRAS, FN, and SMAD3. Conclusions These data establish a positive correlation between NASH–HCC–induced renal injury and the degree of hepatic fibrosis, delineate the attendant histopathological and molecular signatures, and implicate the HRAS–SMAD3–FN axis as a putative mechanistic pathway. The HRAS-HCC mouse model uniquely recapitulates key clinicopathological features of human NASH–HCC complicated by CKD, thereby providing a robust preclinical platform for mechanistic dissection and therapeutic